Nano-pillar-based biosensing device

ABSTRACT

In one example, a device includes a trench formed in a substrate. The trench includes a first end and a second end that are non-collinear. A first plurality of semiconductor pillars is positioned near the first end of the trench and includes integrated light sources. A second plurality of semiconductor pillars is positioned near the second end of the trench and includes integrated photodetectors.

FIELD OF THE DISCLOSURE

The present disclosure relates generally to medical diagnostics andrelates more specifically to nano-pillar-based biosensing devices.

BACKGROUND OF THE DISCLOSURE

The detection and/or monitoring of serious health conditions ofteninvolves performing diagnostics on blood, sweat, or other fluids. Forinstance, once a person has been diagnosed with diabetes, he willtypically need to continuously monitor his blood glucose levels in orderto facilitate insulin intake. In other cases, cancer survivors may needto monitor their blood for particular biomarkers (e.g., proteinmolecules) including receptors or antigens that can indicate arecurrence of the disease. In addition, blood tests such asenzyme-linked immunosorbent assay (ELISA) and reverse transcriptasepolymerase chain reaction (PCR) can quickly identify certain types ofinfectious diseases.

SUMMARY OF THE DISCLOSURE

In one example, a device includes a trench formed in a substrate. Thetrench includes a first end and a second end that are non-collinear. Afirst plurality of semiconductor pillars is positioned near the firstend of the trench and includes integrated light sources. A secondplurality of semiconductor pillars is positioned near the second end ofthe trench and includes integrated photodetectors.

In another example, a device includes a trench formed in a substrate.The trench has an angular shape including at least one bend. A firstplurality of semiconductor pillars is positioned near a first end of thetrench and includes integrated light sources. A second plurality ofsemiconductor pillars is positioned near a second end of the trench andincludes integrated photodetectors. A light blocker positioned insidethe bend.

In another example, a method includes treating a fluid sample with afluorophore that binds to particles in the fluid sample. The sample isthen passed through a trench including a plurality of microfluidicchannels, wherein a first end of the trench includes a first pluralityof pillars having integrated light sources. Contact between theparticles and at least one of the light sources causes the fluorophoreto emit light. Trajectories of the particles are tracked through theplurality of microfluidic channels by detecting the light, using aphotodetector integrated into one of a second plurality of pillarspositioned near a second end of the trench.

BRIEF DESCRIPTION OF THE DRAWINGS

The teachings of the present disclosure can be readily understood byconsidering the following detailed description in conjunction with theaccompanying drawings, in which:

FIG. 1 illustrates a top view of an example biosensing device of thepresent disclosure;

FIG. 2 illustrates cross sectional views of three general examples offunctionalized nano-pillars that may be used in the biosensing device ofFIG. 1;

FIG. 3 illustrates a cross sectional view of one example of anano-pillar that has been configured to emit light;

FIGS. 4A-4C illustrate a cross sectional views of three examples of anano-pillar that have been configured to operate as detectors; and

FIG. 5 is a flow diagram illustrating one example of a method forprocessing a sample.

To facilitate understanding, identical reference numerals have beenused, where possible, to designate identical elements that are common tothe Figures.

DETAILED DESCRIPTION

In one example, a nano-pillar-based biosensing device is disclosed. Asdiscussed above, the detection and/or monitoring of serious healthconditions often involves performing diagnostics on blood, sweat, orother fluids. In many cases, the demand has grown for small, lightweightdevices that can perform these diagnostics, including portable orwearable devices. For instance, continuous monitoring of blood glucoselevels has been facilitated by the availability of portable glucosemeters. However, the diagnoses of many other health conditions requirethat a sample of blood or other fluid, once obtained, be transported toa laboratory or other remote facility for analysis (e.g., with discreteoptical imaging systems, microscopes, or other device). This can delaydiagnoses of time-critical conditions and also compromise the integrityof the sample, leading to inaccurate results.

Examples of the present disclosure provide a portable system-on-chip(SoC) that integrates microfluidic channels with light sources,detectors, and complementary metal-oxide-semiconductor (CMOS) circuitry.By integrating light sources or photodetectors into nano-pillars thatare also capable of sorting proteins (e.g., based on size), a compactdevice can be fabricated for performing biosensing applications. Thedevice can be fabricated as a standalone device that performscollection, processing, and diagnostics on a fluid sample, or the devicecan communicate with a remote portable device (e.g., a smart phone ortablet computer) that includes software for performing diagnostics.

FIG. 1 illustrates a top view of an example biosensing device 100 of thepresent disclosure. As illustrated, the device 100 generally comprises asubstrate 102, a trench 104 formed in the substrate 102, and a lightblocker 106 positioned on the substrate 102, adjacent to the trench 104.

The substrate 102 may comprise, for example, a silicon substrate. Thetrench 104 comprises a recess in the substrate 102, i.e., an area inwhich a portion of the substrate material is removed to form a passage.In one example, the trench 104 has an angular shape, e.g., such that theends of the trench are not collinear. For instance, the trench 104 mayform a right angle, as illustrated in FIG. 1. However, in otherexamples, the angle formed by the trench may be smaller or greater thanninety degrees. In further examples still, the trench 104 may have acurved shaped. In each instance, however, the trench 104 includes atleast one bend or corner 108 at which the passage formed by the trench104 changes direction. In one example, the light blocker 106 ispositioned inside of the corner 108. The light blocker may comprise, forinstance, a layer of metal.

A plurality of nano-pillars 110 is positioned inside the trench 104. Inone example, the nano-pillars 110 comprise silicon-based, nano-scalepillars that extend upward from the recessed surface of the substrate102. The sizing and spacing of the nano-pillars 110 creates a pluralityof microfluidic channels through which a sample fluid (e.g., blood orother fluid) can flow from one end of the trench 104 to the other end.In addition, the sizing of and spacing between the nano-pillars 110 canbe optimized to sort proteins in the sample fluid, e.g., such thatproteins of certain sizes are forced along particular channels of theplurality of microfluidic channels.

In one example, subsets of the nano-pillars 110 are functionalized. Thatis, the subsets include nano-pillars that have been configured toprovide functions in addition to sorting. For instance, the device 100illustrated in FIG. 1 includes two functionalized subsets ofnano-pillars 110. A first subset 112 positioned near a first end of thetrench 104 comprises nano-pillars 110 that include integrated lightsources, such as integrated light emitting diodes (LEDs). The specificwavelength or wavelengths that can be emitted by a given nano-pillar 110may be tuned in one example by adjusting the size of the pillar (e.g.,diameter) and/or the material from which the pillar is fabricated toenable excitation of one or more particular fluorophores. For instance,a nano-pillar 110 integrating an indium gallium nitride-based lightsource may emit light in the 300-400 nanometer wavelength range; anano-pillar 110 integrating a gallium arsenide-based or aluminum galliumarsenide-based light source may emit light in the 700-850 nanometerwavelength range; and a nano-pillar 110 integrating an indium galliumarsenic phosphide-based light source may emit light in the 1310-1550nanometer wavelength range. Thus, the configurations of the nano-pillars110 in the first subset 112 need not be identical, but may includenano-pillars 110 of varying sizes, materials, and configurations. In oneexample, each nano-pillar 110 in the first subset 112 is individuallyaddressable (e.g., by an active matrix or passive matrix circuits) toemit light. One specific example of a nano-pillar including anintegrated light source is discussed in further detail in connectionwith FIG. 3.

A second subset 114 positioned near a second end of the trench 104comprises nano-pillars 110 that include integrated photodetectors thatare tuned to detect light of specific wavelengths. The specificwavelength or wavelengths that can be detected by a given nano-pillar110 may be tuned in one example by adjusting the size of the pillar(e.g., diameter) and/or the material from which the pillar isfabricated. For instance, a nano-pillar 110 integrating an indiumgallium nitride-based photodetector may detect light in the 300-400nanometer wavelength range; a nano-pillar 110 integrating asilicon-based photodetector may detect light in the 400-850 nanometerwavelength range; a nano-pillar 110 integrating a gallium arsenide-basedphotodetector may detect light in the 500-850 nanometer wavelengthrange; and a nano-pillar 110 integrating an indium galliumarsenide-based photodetector may detect light in the 850-1550 nanometerwavelength range. Thus, the configurations of the nano-pillars 110 inthe second subset 114 need not be identical, but may includenano-pillars 110 of varying sizes, materials, and configurations. Somespecific examples of nano-pillars including integrated photodetectorfunctionality are discussed in further detail in connection with FIGS.4A-4C.

In this case, the light blocker 106 is positioned to minimize detectionby the second subset 114 of light emitted by the first subset 112. Theshape of the trench 104 also helps in this respect. As discussed infurther detail below, the first and second subsets 112 and 114 ofnano-pillars 110 allow the device 100 to track particles in a samplefluid, which, in turn, may aid in the detection and diagnosis of certainmedical conditions.

In some examples, the biosensing system 100 can be fabricated as adisposable, one-time-use chip. In this case, a separate reader devicemay be fabricated to analyze data collected by the biosensing system100.

FIG. 2 illustrates cross sectional views of three general examples offunctionalized nano-pillars 200 a-200 c that may be used in thebiosensing device 100 of FIG. 1. Thus, any of the nano-pillars 200 a-200c may be used as the basis for a nano-pillar with integrated lightsource or a nano-pillar with an integrated photodetector, e.g., asillustrated in the first subset 112 and second subset 114 of thenano-pillars 110.

In general, each of the nano-pillars 200 a-200 c is fabricated as ap-i-n diode on a semiconductor substrate 202. In one example, thesemiconductor substrate 202 may be n-doped.

In a first example, the nano-pillar 200 a comprises an undoped,intrinsic layer 204 a fabricated directly on the n-doped substrate 202.A p-doped layer 206 a is then fabricated directly on the intrinsic layer204 a.

In a second example, the nano-pillar 200 b comprises an n-doped layer208 fabricated directly on the n-doped substrate. An undoped, intrinsiclayer 204 b is fabricated directly on the n-doped layer 208. A p-dopedlayer 206 b is then fabricated directly on the intrinsic layer 204 b.

In a third example, the nano-pillar 200 c comprises a pillar of p-dopedmaterial 206 c fabricated directly on the n-doped substrate 202. Thepillar of p-doped material 206 c includes an undoped, intrinsic core 204c.

The configurations illustrated in FIG. 2 may be used to fabricatenano-pillars having integrated light sources (e.g., such as thenano-pillars 110 in the first subset 112 of FIG. 1) or nano-pillarshaving integrated photodetectors (e.g., such as the nano-pillars 110 inthe second subset 114 of FIG. 1). Where the nano-pillars includeintegrated light sources, a light source such as an LED light source maybe fabricated in the intrinsic layer of the p-i-n diode. Where thenano-pillars include integrated photodetectors, the p-i-n diode may formthe photodiode, as described in further detail with respect to FIGS.4A-4C.

FIG. 3 illustrates a cross sectional view of one example of anano-pillar 300 that has been configured to emit light. Thus, thenano-pillar 300 may be used, for instance, in the first subset 112 ofnano-pillars 110 illustrated in FIG. 1.

As illustrated, the nano-pillar 300 is fabricated on a semiconductorsubstrate 302 such as a silicon substrate. The substrate 302 may bepatterned with a series of trenches. The sidewalls of the trenches maybe lined with a layer 304 of insulating material, such as silicondixode. A layer 306 of a semiconductor material, such as germanium, mayline the bottoms of the trenches. A light emitting diode 308, such as anLED formed from one or more Group III-V materials, is grown on the layer306 of semiconductor material.

FIGS. 4A-4C illustrate cross sectional views of three examples ofnano-pillar 400 a-400 c that have been configured to operate asphotodetectors. Thus, the nano-pillar 400 a, 400 b, or 400 c may beused, for instance, in the second subset 114 of nano-pillars 110illustrated in FIG. 1. In each example, the nano-pillar 400 a, 400 b, or400 c is fabricated as a p-i-n photodetector on a semiconductorsubstrate. However, in other examples, the photodetectors may befabricated as p-n diodes, without an intervening intrinsic layer.

Referring to FIG. 4A, the example nano-pillar 400 a is fabricated on asemiconductor substrate 402 a, such as a gallium arsenide substrate. Thesubstrate 402 a may have a thickness of approximately 850 nanometers. Afirst contact 404 a, formed, for example, from an n-type semiconductormaterial such as n+ gallium arsenide is fabricated on the substrate 402a. An absorber layer 406 a, formed, for example, from undoped, intrinsicgallium arsenide, is then fabricated on the first contact 404 a. Asecond contact 408 a, formed, for example, from p+ gallium arsenide, isthen fabricated on absorber layer 406 a. Thus, the first contact 404 a,absorber layer 406 a, and second contact 408 a collectively form agallium arsenide p-i-n diode on a gallium arsenide substrate 402 a.

Referring to FIG. 4B, the example nano-pillar 400 b is fabricated on asemiconductor substrate 402 a, such as a silicon substrate. Thesubstrate 402 b may have a thickness of approximately 850 nanometers. Afirst buffer layer 410 b, formed, for example, from germanium, isfabricated on the substrate 402 b. A second buffer layer 412 b, formed,for example, from indium gallium phosphide, is fabricated on the firstbuffer layer 410 b. A first contact 404 b, formed, for example, from ann-type semiconductor material such as n+ gallium arsenide is fabricatedon the second buffer layer 412 b. An absorber layer 406 b, formed, forexample, from undoped, intrinsic gallium arsenide, is then fabricated onthe first contact 404 b. A second contact 408 b, formed, for example,from p+gallium arsenide, is then fabricated on absorber layer 406 b.Thus, the first contact 404 b, absorber layer 406 b, and second contact408 b collectively form a gallium arsenide p-i-n diode on a siliconsubstrate 402 b (with a multi-layer buffer formed between the p-i-ndiode and the substrate).

Referring to FIG. 4C, the example nano-pillar 400 c is fabricated on asemiconductor substrate 402 c, such as a silicon substrate. Thesubstrate 402 c may have a thickness between approximately 1310 and 1550nanometers. A first buffer layer 410 c, formed, for example, fromgermanium, is fabricated on the substrate 402 c. A second buffer layer412 c, formed, for example, from gallium arsenide, is fabricated on thefirst buffer layer 410 c. A third buffer layer 414 c, formed, forexample, from indium phosphide, is fabricated on the second buffer layer412 c. A first contact 404 c, formed, for example, from an n-typesemiconductor material such as n+ indium gallium arsenide is fabricatedon the third buffer layer 414 c. An absorber layer 406 c, formed, forexample, from undoped, intrinsic indium gallium arsenide, is thenfabricated on the first contact 404 c. A second contact 408 c, formed,for example, from p+ indium gallium arsenide, is then fabricated onabsorber layer 406 c. Thus, the first contact 404 c, absorber layer 406c, and second contact 408 c collectively form an indium gallium arsenidep-i-n diode on a silicon substrate 402 c (with a multi-layer bufferformed between the p-i-n diode and the substrate).

FIG. 5 is a flow diagram illustrating one example of a method 500 forprocessing a sample. The method 500 may be performed, for instance,using the biosensing device 100 illustrated in FIG. 1. As such,reference is made in the discussion of the method 500 to variouselements of FIG. 1. However, it will be appreciated that the method 500could be performed using a device with a configuration that differs fromthe configuration shown in FIG. 1.

The method 500 begins in step 502. In step 504, a sample is obtained. Inone example, the sample is a fluid sample, such as blood or anotherfluid. The sample is to be analyzed for evidence of one or more medicalconditions.

In step 506, the sample is treated with one or more fluorophores (i.e.,fluorescent chemical compounds that emit light upon excitation).Different fluorophores will bind to different particles that may or maynot be present in the sample.

In step 508, the first subset 112 of nano-pillars 110 is activated. Forinstance, the nano-pillars 110 including integrated light sources may beactivated to emit light of one or more wavelengths.

In step 510, the fluorophore-treated sample is passed through the firstend of the trench 104 in the biosensing device 100, such that the samplecomes into contact with the first subset 112 of nano-pillars 110. As theparticles in the sample hit the nano-pillars 110 in the first subset112, the fluorophores that have bound to the particles will becomeexcited and cause the particles to emit fluorescence. The emittedfluorescence will exhibit signatures that are unique to thefluorophores.

In step 512, the second subset 114 of nano-pillars 110 detects thefluorescence emitted by the fluorophore-bound particles. In one example,the position of the light blocker 106 ensures that the light detected bythe second subset 114 of nano-pillars 110 is the fluorescence emitted bythe particles of the sample rather than the light emitted by the lightsources of the first subset 112 of nano-pillars 110.

In step 514, the second subset 114 of nano-pillars 110 tracks thetrajectories of the particles through the trench 104, based on trackingof the emitted fluorescence. That is, because each fluorophore isselected to bind to a specific particle and emits a unique signaturefluorescence when excited, the trajectory taken by the specific particlecan be tracked by detecting and following the emission of the signaturefluorescence.

In step 516, a diagnosis is made based on the tracking of particletrajectories. In particular, particles of different sizes will havedifferent trajectories (e.g., based on the sizing and spacing of thenano-pillars 110, which will force particles of certain sizes alongparticular microfluidic channels). Thus, based on the trajectory, theparticle size can be estimated. Then, based on the particle size, amedical diagnosis may be made (e.g., based on the presence or absence ofparticles of a certain size). The diagnosis may indicate that no medicalconditions of concern are present, or the diagnosis may indicate thepotential presence of a condition that requires medical attention.

The method 500 ends in step 518.

Although various embodiments which incorporate the teachings of thepresent invention have been shown and described in detail herein, thoseskilled in the art can readily devise many other varied embodiments thatstill incorporate these teachings.

What is claimed is:
 1. A method comprising: treating a fluid sample witha fluorophore that binds to particles in the fluid sample; passing thesample through a trench including a plurality of microfluidic channels,wherein a first end of the trench includes a first plurality of pillarshaving integrated light sources, and wherein contact between theparticles and at least one of the light sources causes the fluorophoreto emit light; and tracking trajectories of the particles through theplurality of microfluidic channels by detecting the light, using aphotodetector integrated into one of a second plurality of pillarspositioned near a second end of the trench.
 2. The method of claim 1,further comprising: blocking light emitted by the integrated lightsources from reaching the photodetector.
 3. The method of claim 1,wherein the first end of the trench and the second end of the trench arenon-collinear.
 4. The method of claim 1, wherein the trench has anangular shape including at least one bend.
 5. The method of claim 1,further comprising: sorting the particles from other particles havingdifferent sizes, using a third plurality of pillars positioned betweenthe first plurality of pillars and the second plurality of pillars. 6.The method of claim 1, wherein the first plurality of pillars includespillars of at least two different sizes.
 7. The method of claim 1,wherein the integrated light sources include light sources configured toemit light in at least two different wavelength ranges.
 8. The method ofclaim 1, wherein the second plurality of semiconductor pillars includessemiconductor pillars of at least two different sizes.
 9. The method ofclaim 1, wherein the second plurality of pillars includes a plurality ofintegrated photodetectors, and the plurality of integratedphotodetectors includes photodetectors configured to detect light in atleast two different wavelength ranges.
 10. The method of claim 1,further comprising: making a medical diagnosis based on thetrajectories.
 11. The method of claim 10, wherein making the medicaldiagnosis comprises: estimating sizes of the particles based on thetrajectories; and diagnosing a medical condition based on at least someof the particles being estimated to be of a defined size.
 12. The methodof claim 11, wherein the sizes of the particles are estimated from thetrajectories based on known sizings and spacings of those of theplurality of microfluidic channels through which the particles pass. 13.The method of claim 11, wherein the estimating and the diagnosing areperformed locally on a chip containing the trench, the plurality ofmicrofluidic channels, the first plurality of pillars, and the secondplurality of pillars.
 14. The method of claim 11, wherein the estimatingand the diagnosing are performed by a device that is remote from a chipcontaining the trench, the plurality of microfluidic channels, the firstplurality of pillars, and the second plurality of pillars.
 15. Themethod of claim 10, wherein making the medical diagnosis comprises:estimating sizes of the particles based on the trajectories; anddiagnosing a medical condition based on none of the particles beingestimated to be of a defined size.
 16. The method of claim 15, whereinthe sizes of the particles are estimated from the trajectories based onknown sizings and spacings of those of the plurality of microfluidicchannels through which the particles pass.
 17. The method of claim 15,wherein the estimating and the diagnosing are performed locally on achip containing the trench, the plurality of microfluidic channels, thefirst plurality of pillars, and the second plurality of pillars.
 18. Themethod of claim 15, wherein the estimating and the diagnosing areperformed by a device that is remote from a chip containing the trench,the plurality of microfluidic channels, the first plurality of pillars,and the second plurality of pillars.
 19. The method of claim 1, whereinthe trench, the plurality of microfluidic channels, the first pluralityof pillars, and the second plurality of pillars are contained on aportable system-on-chip.
 20. The method of claim 1, wherein the treatingcomprises treating the fluid sample with a plurality of differentfluorophores, wherein each fluorophore of the plurality of differentfluorophores binds to particles of a different type in the fluid sample.